期刊
ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 5, 页码 6043-6052出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c21223
关键词
DNA methylation; optogenetic; CRISPR-Cas9; NIR light; upconversion
资金
- National Natural Science Foundation of China [81872169]
- Tianjin key research and development program science and technology support key projects [17YFZCSY00690]
- Natural Science Foundation of Tianjin Education Bureau [2018KJ065]
- Initial Foundation of Tianjin Medical University Cancer Institute and Hospital [B1708]
The study developed a novel near-infrared activated DNA methylation editing system using optogenetics, allowing control of DNA methylation editing in response to light, with potential for remote editing.
DNA methylation is a kind of a crucial epigenetic marker orchestrating gene expression, molecular function, and cellular phenotype. However, manipulating the methylation status of specific genes remains challenging. Here, a clustered regularly interspaced palindromic repeats-Cas9-based near-infrared upconversion-activated DNA methylation editing system (CNAMS) was designed for the optogenetic editing of DNA methylation. The fusion proteins of photosensitive CRY2PHR, the catalytic domain of DNMT3A or TET1, and the fusion proteins for CIBN and catalytically inactive Cas9 (dCas9) were engineered. The CNAMS could control DNA methylation editing in response to blue light, thus allowing methylation editing in a spatiotemporal manner. Furthermore, after combination with upconversion nanoparticles, the spectral sensitivity of DNA methylation editing was extended from the blue light to near-infrared (NIR) light, providing the possibility for remote DNA methylation editing. These results demonstrated a meaningful step forward toward realizing the specific editing of DNA methylation, suggesting the wide utility of our CNAMS for functional studies on epigenetic regulation and potential therapeutic strategies for related diseases.
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